Outcomes of a Multicenter 10-Year Review of Postinjection Endophthalmitis and Associated Systemic Medical Comorbidities.

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

A 48-YEAR-OLD WOMAN WITH CHRONIC, PROGRESSIVE BILATERAL VISION LOSS AND DYSPNEA.

PURPOSE: To describe a unique case of isolated, bilateral serous retinal detachments associated with primary pulmonary arterial hypertension. METHODS: Case report. RESULTS: A 48-year-old woman with primary pulmonary arterial hypertension presented with bilateral vision loss. She was found to have bilateral serous retinal detachments in the macula with accumulation of the fibrinous material. Optical coherence tomography demonstrated intraretinal and subretinal fluid, hyperreflective material in the subretinal space, and choroidal engorgement. Fluorescein angiography demonstrated pooling in the maculas, an area of blockage corresponding with the area of subretinal exudative material, and a petalloid pattern of leakage in the maculas without evidence of retinal vascular leakage. Her ocular symptoms improved with aggressive medical management of her pulmonary arterial hypertension with the addition of eplerenone. CONCLUSION: Primary pulmonary arterial hypertension results in chronically elevated systemic venous pressure, leading to both systemic and ocular symptoms. It is important to consider this systemic condition in the differential diagnosis of serous retinal detachments to provide adequate multidisciplinary management.

Late Vitreoretinal Complications of Regressed Retinopathy of Prematurity: Retinal Break, Vitreous Hemorrhage, and Retinal Detachment.

PURPOSE: To investigate late vitreoretinal complications and visual outcomes in patients with regressed retinopathy of prematurity (ROP) with or without prior treatment. DESIGN: International, multicenter, noncomparative retrospective case series. PARTICIPANTS: We analyzed 264 eyes of 238 patients from 13 centers worldwide who developed vitreoretinal complications (retinal detachment [RD], vitreous hemorrhage [VH], or retinal break) ≥ 2 years after resolution of acute ROP. METHODS: Each participant was assigned to 1 of 3 groups (the RD, VH, and retinal break groups) according to their primary diagnosis. The average age at presentation, visual acuities, refractive error, axial length, gestational age, birth weight, acute ROP classification, prior treatments for acute ROP, postoperative visual acuity (VA), and concomitant eye conditions in the 3 groups were documented and compared. MAIN OUTCOME MEASURES: Clinical features and visual outcomes of late vitreoretinal complications in patients with regressed ROP. RESULTS: A total of 264 eyes of 238 patients were included. The prior acute ROP status was comparable among the 3 groups, except that the VH group had a higher proportion of patients with type 1 ROP (P = 0.03) and prior treatment (P < 0.001) than the other groups. The average age at presentation was earlier in the RD (20.3 ± 15.5 years) and VH (21.4 ± 18.9 years) groups than in the retinal break group (31.9 ± 18.2 years; P < 0.001). The retinal break group had the best presenting best-corrected VA, followed by the RD and VH groups (P < 0.001). Surgical intervention improved VA in both the RD and VH groups (both P < 0.05). The overall trend of VA was the most favorable in the retinal break group, followed by that in the VH and RD groups. Cicatricial changes in the fellow retina were observed in > 90% of patients with unilateral involvement. CONCLUSIONS: Infants with acute ROP remain at a high risk of vision-threatening complications throughout childhood and adulthood. Continual follow-up of patients with ROP is important. When severe complications, such as RD or VH, are detected, timely surgical intervention is necessary to ensure favorable visual outcomes in these patients.

Iatrogenic choroidal neovascularization associated with subretinal gene therapy surgery.

Purpose: To report a case of iatrogenic choroidal neovascularization (CNV) developing one month after subretinal gene therapy surgery. Observations: A 16-year-old male with biallelic RPE65 mutation associated retinal dystrophy was treated with subretinal voretigene neparvovec in the left eye. During initiation of a balanced salt solution pre-bleb, a faint and transient subretinal hemorrhage was observed at the retinotomy site. One month post-operatively, multi-modal imaging detected a CNV and a break in Bruch's membrane at the retinotomy site. The asymptomatic CNV was observed without treatment and resolved spontaneously. Conclusions & importance: As subretinal gene therapy surgery becomes more common, clinicians should monitor for possible trauma induced CNV associated with retinotomy formation and subretinal injection.

Spontaneous rupture of secondary iris inclusion cyst causing acute glaucoma and other ocular sequelae.

A 63-year-old woman with a known secondary iris inclusion cyst in her right eye presented with headache, blurry vision, and eye pain of 3 days' duration. Initial findings were notable for significant decrease in vision and elevated intraocular pressure in the right eye, with diffuse microcystic corneal edema, diffuse anterior chamber flare with minimal cellular reaction, and a significantly decompressed iris inclusion cyst. On gonioscopy, the right eye was open to scleral spur, and no pigment was visualized. Patient history and presentation were consistent with a diagnosis of spontaneous rupture of iris inclusion cyst causing secondary glaucoma. Iris inclusion cysts are not uncommon; however, ocular outcomes are generally benign and limited to obstruction of the pupillary axis.

Retinopathy and Systemic Disease Morbidity in Severe COVID-19.

PURPOSE: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19. DESIGN: Retrospective, observational cohort study. METHODS: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy. RESULTS: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, p = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors (p < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy (p = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, p = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, p = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, p = .04). CONCLUSION: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.

Cell Phone Selfies: Clinching the Diagnosis of Iris Microhemangiomatosis.

Four patients presented with a history of "blood" or a "dark spot" in the eye captured on cell phone photos. These episodes prompted presentation to an ophthalmologist where they all had normal slit lamp exams without a hyphema at initial evaluation. With evidence of a spontaneous hyphema seen on photos, further testing was performed including iris fluorescein angiography which revealed hyperfluorescent iris margin vascular tufts, confirming the diagnosis of iris microhemangiomatosis in each patient. All cases were managed conservatively, and only 1 needed topical antihypertensives. Without these patient-initiated photos, the diagnosis of iris microhemangiomatosis would likely remain elusive as slit lamp exam was normal at the time of initial examination in all 4 cases. Ophthalmologists should be aware of this rare diagnosis in the event a patient comes with a cell phone selfie documenting a spontaneous hyphema, especially when emanating from pupillary border.

Suprachoroidal Injection of Triamcinolone- Review of a Novel Treatment for Macular Edema Caused by Noninfectious Uveitis.

Macular edema is the most frequent cause of visual deterioration in noninfectious uveitis. The treatment of noninfectious uveitis with associated macular edema commonly includes systemic or locally administered corticosteroids, with long-term use limited by significant side effects. The need for a treatment with an improved safety profile has driven the development of a novel ophthalmic therapy: a proprietary triamcinolone acetonide suspension (CLS-TA) administered in the suprachoroidal space (XIPERE™; Clearside Biomedical, Alpharetta, GA, USA). Suprachoroidal delivery of corticosteroids allows higher steroid concentration in the posterior segment and decreases the risk of other adverse ocular events. Recent results from the PEACHTREE trial (ClinicalTrials.gov Identifier: NCT02595398), a phase III trial with two suprachoroidal injections of CLS-TA at 0 and 12 weeks with follow up lasting 24 weeks, showed the significant improvement in visual acuity and reduction in central subfield thickness, all without increasing the risk of elevated intraocular pressure or accelerated cataract progression.

Ocular Involvement in Patients with Fungemia in an Urban Tertiary Care Center.

PURPOSE: To illustrate the rate of endogenous endophthalmitis associated with fungemia and evaluate the importance of screening in a public city hospital. METHODS: A retrospective review was performed on all inpatient ophthalmology consults for fungemia from 2010 to 2015. Clinical histories, ocular examinations, and microbial cultures were reviewed. RESULTS: Of 95 patients (mean age 51.6 years, 75% male) with fungemia, 9/95 (9.5%) demonstrated intraocular involvement. Of these nine patients, two were unable to participate in the ophthalmic exam due to intubation, while the remaining seven reported no changes in their vision. Two patients had their antifungal medications adjusted to optimize intraocular penetration and one patient progressed to develop vitreous involvement but died before further escalation of care occurred. CONCLUSION: All involved individuals in this study were either non-communicative or without visual complaints. This suggests that routine screening should still be recommended, especially in a public hospital setting.

Vascular changes on fluorescein angiography of premature infants with low risk of retinopathy of prematurity after high oxygen exposure.

PURPOSE: To describe a wide array of peripheral vascular changes using fluorescein angiography in preterm neonates, without high risk characteristics for developing retinopathy of prematurity, that were exposed to high oxygen concentration. METHODS: Retrospective, two center, case series. Newborns at two different hospitals with ≥1500 g or gestational age of ≥32 weeks, fluorescein angiography performed, and with high oxygen exposure without adequate control were included. RESULTS: 294 infants diagnosed with ROP were analyzed. Only 28 eyes from 14 patients with peripheral vascular abnormalities in older and heavier babies were included. Two distinct type of peripheral vascular changes were observed: group 1 or non-proliferative: areas of capillary non-perfusion along with widespread arteriovenous shunting between adjacent primary vessels, tortuosity of primary vessels, abnormal budding of tertiary vessels and capillaries, abnormal capillary tufts and absence of foveal avascular zone; group 2 or proliferative: all of the characteristics of group 1 plus leakage of dye from the boundary between perfused and non-perfused retina and/or optic disc. CONCLUSION: Peripheral vascular abnormalities different from retinopathy of prematurity are observed in older than 32 weeks of gestational age, and heavier than 1500 g babies. This makes the authors classify these patients as having a disease caused solely by oxygen dysregulation at the neonatal intensive care unit similarly to the oxygen induced retinopathy in experimental studies.

Changes in the Eye Microbiota Associated with Contact Lens Wearing.

UNLABELLED: Wearing contact lenses has been identified as a risk factor for the development of eye conditions such as giant papillary conjunctivitis and keratitis. We hypothesized that wearing contact lenses is associated with changes in the ocular microbiota. We compared the bacterial communities of the conjunctiva and skin under the eye from 58 subjects and analyzed samples from 20 subjects (9 lens wearers and 11 non-lens wearers) taken at 3 time points using a 16S rRNA gene-based sequencing technique (V4 region; Illumina MiSeq). We found that using anesthetic eye drops before sampling decreases the detected ocular microbiota diversity. Compared to those from non-lens wearers, dry conjunctival swabs from lens wearers had more variable and skin-like bacterial community structures (UniFrac;P value = <0.001), with higher abundances of Methylobacterium,Lactobacillus,Acinetobacter, andPseudomonasand lower abundances of Haemophilus,Streptococcus,Staphylococcus, and Corynebacterium(linear discriminant analysis [LDA] score = >3.0). The results indicate that wearing contact lenses alters the microbial structure of the ocular conjunctiva, making it more similar to that of the skin microbiota. Further research is needed to determine whether the microbiome structure provides less protection from ocular infections. IMPORTANCE: As in other body sites (i.e., the gut, skin, and mouth), the eye has a normal community of bacteria which are expected to confer resistance that provides protection from invaders. However, the eye microbiome has been largely neglected and is relevant to eye health and understanding eye diseases and to discovery of its functions. This report of a baseline study shows differences in the eye microbiome of contact lens wearers in relation to those of non-lens wearers and has the potential to help future studies explore novel insights into a possible role of the microbiome in the increased risk for eye infections in contact lens wearers.

Synthesis of a C-linked hyaluronic acid disaccharide mimetic.

The synthesis of a C-disaccharide that is designed as a mimetic for the repeating unit disaccharide of hyaluronic acid is described. The target compound was obtained via the SmI2-promoted coupling reaction of the sulfone, 2-acetamido-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1,2-dideoxy-1-pyridinylsulfonyl-beta-D-glucopyranose (6), and the aldehyde, p-methoxyphenyl 2,3-di-O-benzyl-4-deoxy-4-C-formyl-6-O-p-methoxybenzyl-beta-D-glucopyranoside (14).

Withholding inputs in team contexts: member composition, interaction processes, evaluation structure, and social loafing.

Social loafing was observed as a naturally occurring process in project teams of students working together for 3-4 months. The authors assessed the contributions that member composition (i.e., relational dissimilarity and knowledge, skills, and abilities; KSAs), perceptions of the team's interaction processes (i.e., dispensability and the fairness of the decision-making procedures), and the team's evaluation structure (i.e., identifiability) make toward understanding loafing behavior. Identifiability moderated the impact of dispensability on loafing but not the impact of fairness on loafing. Perceptions of fairness were negatively related to the extent that participants loafed within their team. Specific aspects of relational dissimilarity were positively associated with perceptions of dispensability and negatively associated with perceptions of fairness, whereas KSAs were negatively associated with perceptions of dispensability.

Development of a statewide hospital plan for radiologic emergencies.

Although general guidelines have been developed for triage of victims in the field and for hospitals to plan for a radiologic event, specific information for clinicians and administrators is not available for guidance in efficient management of radiation victims during their early encounter in the hospital. A consensus document was developed by staff members of four Connecticut hospitals, two institutions of higher learning, and the State of Connecticut Department of Environmental Protection and Office of Emergency Preparedness, with assistance of the American Society for Therapeutic Radiology and Oncology. The objective was to write a practical manual for clinicians (including radiation oncologists, emergency room physicians, and nursing staff), hospital administrators, radiation safety officers, and other individuals knowledgeable in radiation monitoring that would be useful for evaluation and management of radiation injury. The rationale for and process by which the radiation response plan was developed and implemented in the State of Connecticut are reviewed. Hospital admission pathways are described, based on classification of victims as exposed, contaminated, and/or physically injured. This manual will be of value to those involved in planning the health care response to a radiologic event.

A review of intrathecal morphine therapy related granulomas.

The development of catheter associated granulomatous masses in intrathecal morphine therapy is an uncommon, but potentially serious problem. While these systems have historically been used in patients with short life expectancies, more recently patients with pain from a benign source have benefited from this therapy, and new complications are being encountered secondary to the patients' longer life spans. Morphine is the most commonly used intrathecal opioid and evidence exists that the formation of granulomatous masses are related to the use of higher doses. When the patients' requirement of morphine increases significantly, the physician should be alert for signs of spinal cord compression, such as new neurological deficits, myelopathy, or radiculopathy. Patients that require these higher doses should be properly informed of the association with granulomas and their associated risks. Indolent infection may also be the etiology of granulomatous masses, and the presence of organisms, both aerobic and anaerobic, should be routinely investigated. Patients with catheter-associated granulomas appear to share several features. They exhibit the onset of symptoms several months following the initiation of intraspinal opioids and commonly present with an increase in pain that precedes signs and symptoms of neurological deterioration. While MRI might be the preferred method of detection of intrathecal granulomas, its cost and availability are prohibitive for routine screening. CT myelogram via pump side port injection of contrast can also be performed to detect catheter tip related granulomas/obstructions. Serial neurological examinations for new deficits may be performed and recorded during pump refill visits to recognize a granulomatous mass in its early stages. If an abnormality is identified, imaging studies are appropriate. Awareness of the condition and vigilance are the keys to successful management of this complication.

Intrathecal morphine therapy related granulomas: two case reports.

Intrathecal morphine infusions have historically been used in patients with short life expectancies. More recently, patients with pain from a benign source have benefited from this therapy. While use in this population has been well documented and found to be relatively safe, new complications are being encountered secondary to the patients' longer life spans. The development of granulomatous masses from catheter use in intrathecal morphine therapy is an uncommon, but potentially serious problem. At West Virginia University Hospital, we have implanted more than 700 intrathecal drug delivery systems (IT-DDS) since 1989, and have encountered two cases of granulomatous masses developing at the tip of the intrathecal catheter. This report describes these illustrative cases and provides a review of the literature.

A Concise, Enantioselective Synthesis of (-)- and (+)-Hongconin.

Optically pure enone 9c, available in three steps from known 6-deoxy D-galactal derivative 7b, reacts with cyanophthalide 6 to directly afford the natural product (-)-hongconin (1), a compound from traditional Chinese medicine recently shown to exhibit antianginal activity. The enantiomer of 1 and its (+)-cis-diastereomer were also synthesized in a parallel fashion from the L-sugar counterpart. The use of C-glycoside Michael acceptors, as opposed to their O-glycoside counterparts, represents a potentially useful simplification of phthalide annulation methodology in synthesizing numerous other such optically pure isochromanquinoids, since it obviates the inconvenience of additional steps late in the synthetic scheme associated with reductive manipulation of a remaining acetal moiety into the desired pyran ring substituent.